Description: (provided by the applicant) Stroke is the leading cause of disability in older Americans. Each year, 750,000 Americans suffer a stroke, two-thirds of which are left with chronic neurological deficits that impair function. Principal among them is hemiparetic gait, which impairs mobility and propagates disability by physical deconditioning and learned non-use. Based on emerging evidence that repetitive forced-use training can improve paretic upper extremity function even years after a disabling stroke, we investigated treadmill exercise as a task-oriented training modality to optimize locomotor re-learning, while eliciting cardiovascular conditioning in chronically disabled stroke patients. These studies provide the first evidence that treadmill training increases V02 peak and lowers extremity motor control to improve functional mobility after stroke. Both central and peripheral neuromuscular mechanisms may contribute to improved function with exercise after stroke. We have developed the first functional magnetic resonance imaging (fMRI) protocol to examine brain activation during knee movement, and novel transcranial magnetic stimulation (TMS) methodology enabling non-invasive study of CNS motor control of the quadriceps muscles. These new methods for studying neural plasticity are proposed in concert with measures of paretic leg-muscle mass and metabolism to identify the neuromuscular mechanisms underlying functional gains with treadmill training after stroke. This randomized study tests the hypothesis that six months of treadmill training will improve fitness and functional mobility in chronic hemiparetic stroke patients by mechanisms that both alter neural plasticity and improve skeletal muscle mass and metabolism in the paretic leg. The specific aims are to: (1) Determine the effects of treadmill training on functional mobility and fitness by measuring gait economy, V02 peak, and human performance of gait, stepping, and balance; (2) Determine the mechanism(s) underlying the functional mobility adaptations achieved during treadmill training by measuring lower extremity strength and spasticity, muscle mass and metabolism, and neural plasticity using TMS and fMRI; and (3) Ascertain whether the anticipated gains in cardiovascular fitness and motor control with six months of treadmill training translate into improved long-term functional independence in the home-community setting by tracking ADL profiles and free-living ambulatory activity levels over a subsequent six-month maintenance exercise training program. Results of this IDS will provide the knowledge to consider a larger community based clinical trial to establish the effectiveness of task-oriented exercise to improve functionality, long-term health outcomes, quality of life, and to reduce health care costs in the chronic stroke population.